Carnosine for Autism – an Alternative to N-Acetylcysteine (NAC)? or is it Complementary?

Several people have mentioned to me a supplement called L-Carnosine, so I thought it was worthy of its own post.

The first thing to note is lots of supplements have very similar names and indeed two entirely different substances are abbreviated to NAC.

·        Carnosine

·        Carnitine

·        L-Carnosine

·        L-Carnitine

·        N-Acetylcysteine    (abbreviated to “NAC”)

·        N-Acetylcarnosine  (also abbreviated to “NAC”)

In this blog, and in most literature on autism, NAC refers to N-Acetylcysteine.

This post is about Carnosine and L-Carnosine, but there is also research on the use of Carnitine and L-Carnitine regarding autism and Retts syndrome.  So double check what is on the label, if you do indeed order some.

Vladimir Gulevich, Carnosine (and Carnitine)

Vladimir Gulevich  received the degree of doctor of medicine in 1896 from the department of medicine of Moscow State University. From 1900, he rejoined the Moscow State University where he was rector for a brief period of time in 1919. He was a full member of the USSR Academy of Sciences since 1929.

Gulevich discovered both Carnosine and Carnitine in his work in Moscow.  Even today his university is a centre of research for both these substances.

Carnitine and carnosine are composed of the root word carn, meaning flesh, alluding to its prevalence in animal protein. A vegetarian (especially vegan) diet is deficient in adequate carnosine, compared to levels found in a standard diet.

Researchers in Britain, South Korea, Russia and other countries have shown that carnosine has a number of antioxidant properties that may be beneficial.

Carnosine has been proven to scavenge reactive oxygen species (ROS) as well as alpha-beta unsaturated aldehydes formed from peroxidation of cell membrane fatty acids during oxidative stress.

Carnosine can chelate divalent metal ions.  DAN Doctors probably do not know what divalent means, but in Hg²⁺ the “2” means divalent and Hg means mercury.

Carnosine was found to inhibit diabetic nephropathy.

Carnosine-containing products are also used in topical preparations to reduce wrinkles on the skin.

Some studies have detected beneficial effects of N-acetylcarnosine in preventing and treating cataracts of the eyes.

Carnosine and Autism

Small studies, including this one by Michael Chez, have shown the benefit of L-carnosine in autism.  By the way, Chez seems to be one of the handful of genuinely knowledgeable autism clinicians anywhere on the planet.

Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders.

Abstract

L-Carnosine, a dipeptide, can enhance frontal lobe function or be neuroprotective. It can also correlate with gamma-aminobutyric acid (GABA)-homocarnosine interaction, with possible anticonvulsive effects. We investigated 31 children with autistic spectrum disorders in an 8-week, double-blinded study to determine if 800 mg L-carnosine daily would result in observable changes versus placebo. Outcome measures were the Childhood Autism Rating Scale, the Gilliam Autism Rating Scale, the Expressive and Receptive One-Word Picture Vocabulary tests, and Clinical Global Impressions of Change. Children on placebo did not show statistically significant changes. After 8 weeks on L-carnosine, children showed statistically significant improvements on the Gilliam Autism Rating Scale (total score and the Behavior, Socialization, and Communication subscales) and the Receptive One-Word Picture Vocabulary test (all P < .05). Improved trends were noted on other outcome measures. Although the mechanism of action of L-carnosine is not well understood, it may enhance neurologic function, perhaps in the enterorhinal or temporal cortex.

As Dr Chez points out, nobody is 100% certain why it is of benefit.  It could just be the anti-oxidant properties of carnosine or it could be something related to the interaction between carnosine and GABA in the brain.  GABA is an important neurotransmitter in the brain.

Other GABA related drugs show a positive effect in types of autism.  These include Baclofen, Arbaclofen, Bumetanide, Clonazepam and even Valproic acid (VPA).  The underlying mechanisms do differ, but all relate, in one way or the other, to GABA.

The Carnosine dosage used by Dr Chez was 800mg per day.

The body deploys a range of enzymes, called carnosinases, to break down carnosine.  In order to maximize the effect, and out-smart the  carnosinases, it might be wise to split the dose into two per day.

In a perfect world it might be simpler to inhibit the carnosinases and just rely on the carnosine from meat in the diet.

You cannot patent naturally occurring substances, so nobody can patent carnosine and no drug firm will therefore research it.  A carnosinase inhibitor could be patented and therefore could be made into a drug.

Carnosine and GABA

It looks like Moscow State University is still the centre of knowledge for Carnosine and Alexander A. Boldyrev recently published a book called:-

Carnosine and Oxidative Stress in Cells and Tissues

Book Description:

The main aim of this new book is to summarize the knowledge on the metabolic transformation of carnosine in excitable tissues of animals and human beings and to analyze the nature of its biological activity. At the beginning of monograph, the short history of the problem is stated. Distribution of carnosine in tissues, its appearance in ontogeny of vertebrates and correlation between carnosine content and functional activity of tissues are discussed. Chemical properties of carnosine and its natural derivatives and their ability to bind heavy metals and protons in water solution are documented. Special attention is paid to free radical quenching ability and to anti-glycating action. Biological activity of carnosine and carnosine containing compounds was tested using biological models of several levels of complexity, starting from individual enzymes and acellular mixtures and finishing to living cells and survival animals. Effects of carnosine on the whole animals under ischemic, hypoxic and other extreme conditions are described. In conclusion, the ability of carnosine to protect brain and muscular tissues from oxidative injury during exhausting exercise, extreme loading or neurodegenerative diseases is demonstrated. Based on these properties, carnosine is postulated to be a potent protector of human beings from oxidative stress.

You can preview much of the book on Google Books

We know from many autism researchers that oxidative stress is a feature of many people’s autism.  Anything that reduces this stress should have a positive effect on behaviour.

Common antioxidants used in autism include:-

·        N-Acetlycysteine (NAC)

·        Alpha Lipoic Acid (ALA)

·        All the many “chelating” substances used by DAN Doctors

Carnosine may be just an alternative anti-oxidant.

However, when you look through Boldyrev’s book, it does look possible that the chemical relationship between GABA and Carnosine many also play a role.

Conclusion

People currently taking Carnosine for Autism might well want to try N-Acetlycysteine (NAC) and see if they notice an additional benefit.  Conversely, the current NAC converts, like my son Monty, aged 11 with ASD, may well want to give Carnosine a try and see what happens.

One blog reader with Asperger’s finds Baclofen highly beneficial; he might as well give Carnosine a try, based on the GABA relationship.

Current research indicates 2,400 mg of NAC and 800 mg of Carnosine. 

It would be nice if one day somebody would do a controlled trial of NAC vs Carnosine vs Carnosine+NAC;  but don’t hold your breath.

Some people with diabetes are already taking ALA (Alpha lipoic acid) or Thioctacid for neuropathy, but find it also increases insulin sensitivity; this means they need less insulin.  They might well find both NAC and Carnosine will further increase insulin sensitivity.  Generally speaking it seems that low insulin sensitivity is bad and high insulin sensitivity is good; but I am no expert on diabetes.

In some counties Carnosine is not available, but you simply can buy it online on Amazon, ebay or many other sites. 

More on Carnosine from Harvard Medical School